INTERFERON-ALPHA-2B ENHANCES THE NATURAL-KILLER ACTIVITY OF PATIENTS WITH TRANSITIONAL-CELL CARCINOMA OF THE BLADDER

Background. Transitional cell carcinoma (TCC) of the bladder is associ ated with alterations in the immune system of the host. The authors de monstrated that in patients with bladder carcinoma there is a negative correlation between the levels of natural killer (NK) activity and th e clinical evolution and pathologic stages of disease. Methods. The au thors investigated the effect of various doses of recombinant interfer on-alpha-2b (IFN-alpha-2b) for variable periods of culture on the nonm ajor histocompatibility-restricted cytotoxic activity of peripheral bl ood mononuclear cells (PBMNC) with or without CD16 and CD3-depleted po pulations from patients with superficial (confined to the mucosa or la mina propria) and infiltrative (those infiltrating beyond the lamina p ropria) TCC of the bladder using 4-hour 51-sodium chromate (Cr-51)-rel ease cytotoxicity assays against both NK-sensitive (K562) and NK-resis tant (JY) tumor target cells. Results. The normal NK activity detected in PBMNC from patients with superficial TCC of the bladder can be sig nificantly enhanced by short-term (18-hour) incubation with recombinan t IFN-alpha (P < 0.05). The depressed NK cytotoxic activity found in P BMNC from patients with infiltrative TCC can also be significantly enh anced, but not normalized, by short-term (18-hour) incubation with rec ombinant IFN-alpha (P < 0.05). Short-term recombinant IFN-alpha-incuba ted PBMNC from patients with superficial, but not infiltrative, TCC of the bladder also showed marked cytotoxic activity against NK-resistan t target cells. By selection with CD16 or CD3 monoclonal antibodies an d complement, it was also found that the precursor and effector lympho cytes of this recombinant IFN-alpha-promoted cytotoxicity belong to NK lineage. In kinetic studies, it was found that the maximal levels of the recombinant IFN-alpha-promoted cytotoxic activity against NK-sensi tive and NK-resistant target cells in PBMNC from patients with TCC wer e reached after 18 hours of culture. Conclusion. Recombinant IFN-alpha can enhance the nonmajor histocompatibility-restricted cytotoxic acti vity of PBMNC from patients with TCC of the bladder.